Poly(ethylene glycol)-block-poly(L-lactide) (PEG/PLA) Encapsulation of Oral Antibiotics for Drug Delivery into Dentin Tubules Michael Lau 1 , Ridwan Haseeb 1 ,Lucas Rodriguez 1 , Francisco Montagner 2 , Kelli Palmer 3 , Mihaela C.Stefan 1 , Danieli Rodrigues 1 : 1 Department of Bioengineering, University of Texas at Dallas, Richardson, TX; 2 Department of Conservative Dentistry, Federal University of Rio Grande do Sul, Brazil; 3 Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX Aim: To encapsulate an effective drug in oral applications with PEG/PLA diblock copolymer into microparticles for infected root canals and dentinal tubules. To maintain drug release for extended periods to prevent bacterial regrowth after root canal treatment. Methodology: Drug encapsulation was carried out through an oil-water emulsion-solvent evaporation method. In summary, the PEG/PLA copolymer and the oral drug were dissolved in an oil phase (dichloromethane), which was combined and emulsified with a water phase (polyvinyl alcohol and de-ionized water). The resultant solution was stirred, centrifuged, washed, and lyophilized. Particle size was determined using digital microscopy. Antimicrobial effectiveness was assessed in vitro by placing small amounts of encapsulated particles on bacterial (Enterococcus faecalis OG1RF) agar plate cultures and monitoring growth inhibition. Results: Encapsulated particles ranged in size from 2.0 m to 6.5 m, which depended on the homogenization speed employed. Only particles with diameter ≤2.0 m were used for further testing. A preliminary 24-hour bacterial inhibition test showed that the particles exhibited zones of inhibition between 3 mm and 5 mm. Conclusion: The proposed method with the PEG/PLA copolymer effectively encapsulates the oral antibiotic producing particles with size distribution that may penetrate the dentin tubules (2.5 m in diameter). Bacterial inhibition tests showed that the particles inhibited bacterial growth after 24 hours. Ongoing bacterial inhibition tests will determine the extended release profile of the microparticles. This research was supported by the University of Texas at Dallas startup funds (Dr. Rodrigues). Academic Level of First Author: Undergraduate Student Abstract Topic: Bioengineering
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Poly(ethylene glycol)-block-poly(L-lactide) (PEG/PLA) Encapsulation of Oral
Antibiotics for Drug Delivery into Dentin Tubules
Michael Lau1, Ridwan Haseeb
1,Lucas Rodriguez
1, Francisco Montagner
2, Kelli
Palmer3, Mihaela C.Stefan
1, Danieli Rodrigues
1:
1Department of Bioengineering,
University of Texas at Dallas, Richardson, TX; 2Department of Conservative
Dentistry, Federal University of Rio Grande do Sul, Brazil; 3Department of
Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX
Aim: To encapsulate an effective drug in oral applications with PEG/PLA diblock copolymer
into microparticles for infected root canals and dentinal tubules. To maintain drug release for
extended periods to prevent bacterial regrowth after root canal treatment.
Methodology: Drug encapsulation was carried out through an oil-water emulsion-solvent
evaporation method. In summary, the PEG/PLA copolymer and the oral drug were dissolved in
an oil phase (dichloromethane), which was combined and emulsified with a water phase
(polyvinyl alcohol and de-ionized water). The resultant solution was stirred, centrifuged, washed,
and lyophilized. Particle size was determined using digital microscopy. Antimicrobial
effectiveness was assessed in vitro by placing small amounts of encapsulated particles on
bacterial (Enterococcus faecalis OG1RF) agar plate cultures and monitoring growth inhibition.
Results: Encapsulated particles ranged in size from 2.0 m to 6.5 m, which depended on the
homogenization speed employed. Only particles with diameter ≤2.0 m were used for further
testing. A preliminary 24-hour bacterial inhibition test showed that the particles exhibited zones
of inhibition between 3 mm and 5 mm.
Conclusion: The proposed method with the PEG/PLA copolymer effectively encapsulates the
oral antibiotic producing particles with size distribution that may penetrate the dentin tubules
(2.5 m in diameter). Bacterial inhibition tests showed that the particles inhibited bacterial
growth after 24 hours. Ongoing bacterial inhibition tests will determine the extended release
profile of the microparticles.
This research was supported by the University of Texas at Dallas startup funds (Dr. Rodrigues).
Academic Level of First Author: Undergraduate Student
Abstract Topic: Bioengineering
John Corbett
IEEE Medical Device Symposium 2013 Abstract
Lipocalin-type prostaglandin D synthase (L-PGDS) in cerebrospinal fluid (CSF) contributes to the
maturation and maintenance of CNS. L-PGDS post-translational dysregulation may contribute to
pathobiology of different CNS diseases, but methods to monitor its proteoforms are limited. In this
report we combined in-solution isoelectric focusing (IEF) and superficially porous liquid chromatography
(SPLC) with Fourier transform mass spectrometry (FTMS) to characterize common CSF L-PGDS
proteoforms. Across 3D physiochemical space (pI, hydrophobicity, and mass) 217 putative proteoforms
were observed from 21-24 kDa and pI 5-10. Glycoprotein accurate mass information, combined with
tandem MS analysis of peptides generated from 2D fractionated proteoforms, enabled the putative
assignment of 208 proteoforms with varied PTM positional occupants. 15 structurally-related N-glycans
at N29 and N56 were observed, with results that suggest distinct N-glycan compositional variants are
preferred on each amino acid, and that sialic acid content was a determinant of proteoform pI. Other
PTMs characterized include a core-1 HexHexNAc-O-glycan at S7, acetylation at K16 and K138,
sulfonation at S41 and T142, and dioxidation at C43 and C145. The IEF-SPLC-MS platform presented
provides 30-40× improved peak capacity versus conventional 2D gel electrophoresis and shows potential
for repeatable proteoform analysis of surrogate PTM-based biomarkers from biofluids.
Second Annual IEEE Medical Device Symposium “Medical Device Innovation in 21st Century”
The University of Texas at Dallas, Richardson, TX.
Development of methodologies to evaluate the effect of bacterial biofilm and micromotion on corrosion of dental implants *Anie Thomas1, Sathyanarayanan Sridhar1, Arvind Adapalli1 , Maria Burbano-Salazar 1, Sutton Wheelis1, , Kelli Palmer2, Pilar Valderrama3, Thomas G. Wilson3, Danieli Rodrigues1. Introduction: Bacterial biofilms on the surface of dental implants can create byproducts that are acidic in nature. This along with micromotion from occlusal loading, can cause the dissolution of titanium, which is a primary factor of peri-implantitis (PI). Aims & Methods: This study will discuss a novel testing method that will enable the accruement of knowledge on the effect of bacterial biofilm and occlusal forces in the failure of dental implants. Different bacterial strains pertaining to PI, such as E. faecalis, S. sanguinis, S. gordonii, etc., were tested for their growth and pH. The strain capable of providing a good growth rate and an acidic pH, was used for the immersion tests and mechanical testing. In the immersion tests, dental implants were immersed in broth containing the bacterial strain. For mechanical testing the dental implants were placed under fatigue cycles in the presence of bacterial biofilm in a chamber with ample flow of broth and bacteria. The testing conditions were guided by ISO standards which required an inclination of the implant setup at a 30o angle and representation of 3mm bone loss. During immersion and mechanical testing, aliquots from fixed intervals were extracted to quantify the dissolution of titanium ions using Electrical Impedance Spectroscopy and Voltammetry. Surfaces of implants were imaged using a Keyence microscope, and analyzed by Scanning Electron Microscopy equipped with Energy Dispersive X-ray Spectroscopy detector, before and after testing. Results & Conclusion: This experimental setup enacts relevant physiological conditions and forces met in the oral cavity by the implants. Analysis of results show the corrosive nature and forces implants have to endure. The results concluded provides more insight on the contribution of bacterial biofilms and occlusal forces on the integrity of dental implants. Furthermore, targeted measures on how to prevent such factors can also be inferred.
Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080
The goal of the project is the demonstration of a bio-electrochemical solution for quantification of protein biomarker activity from cancer stem cell lysates. This quantification is essential for cancer risk assessment, prognosis study, early diagnosis and phenotype classification. Introduction: Cancer stem cells have been identified as critical cues for detection and analysis of primary cancer metastasis and distant metastasis. It was recently demonstrated that cancer stem cells are rich in aldehyde dehydrogenase isozymes. Current detection/quantification techniques such as western blotting and flow cytometry are not geared for this task due to (1) low concentration of activity markers corresponding to cancer stem cells in a tumor mass (2) lack of robust surface markers. Aims and Methods: This project innovatively combines a nano-porous sieve and micro-metal electrodes for protein biomarker quantification from cancer stem cell lysates. An affinity immunoassay is used to capture specific protein biomarkers and electrochemical impedance spectroscopy is used to quantify these protein-binding events. The nano-porous sieve is overlaid on the electrodes and the resulting innovation (1) achieves improved macromolecular crowding to enhance protein-protein interaction (2) functions as a molecular sieve to filter cell debris, thus reducing non-specific binding/signal (3) achieves an amplified signal response enabling low detection limits. By tuning the frequency of applied voltage, we selectively study the nano-confined spaces where protein binding happens and this additionally helps to achieve low limits of detection.
Results: We present our work for quantification of two isozymes of aldehyde
dehydrogenase: ALDH1A1 and ALDH1A3 from lung cancer stem cell lysates. The sensor has
demonstrated low detection limits of 10 pg/mL for both the protein biomarkers ALDH1A1
and ALDH1A3. This high sensitivity and robust operation showcase the ability of the
technology to be used as a point-of-care solution for quantification of cancer stem cell
activity
Preventing Operating Room Fires: Development of an Operating Room Fire Prevention Device
Aris J. Maguddayao1*, Bradley A. Kimbrough
2, Sarah Luna
1, William C. Culp, Jr. M.D.
3,4
1 University of Texas at Austin, Austin, Texas
2 Baylor University, Waco, Texas
3 Department of Anesthesiology, Scott
& White Hospital, Temple, Texas 4
Texas A&M Health Science Center College of Medicine, Temple, Texas
Gecko Hands: Novel cardiothoracic forceps for prevention of mechanical damage during CABG surgery 1,2Reit, R.*, 2Barrenechea, A., 2Malinow, R., 2Moran, S. 1.Texas Biomedical Device Center, Dallas TX 2.Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta GA *[email protected] Introduction: Coronary heart disease (CHD) is a chronic disease affecting millions of Americans. For individuals with severe CHD, coronary artery bypass graft (CABG) surgery is often the only effective intervention. During a CABG procedure, cardiothoracic surgeons use forceps with broad blades mainly used for tissue manipulation via a compressive force. When manipulating fragile tissues encountered in CABG surgery, forceps can cause unintended damage to the tissue. In this study, novel cardiothoracic forceps which circumvent the application of compressive force to cardiac tissue were explored and prototyped. Aims and Methods: The functional redesign of the cardiothoracic forceps calls for a device with similar design parameters. Novel improvements should ensure the release of tissue in the event of a major displacement (aberrant beat, etc.) to avoid forces above the burst limit of the vessel. Surgeons at Emory University Hospital at Midtown were contacted for input on design parameters and functionality. Calculations on blood vessel rupture force were derived from literature and a handicap factor (E’ = E*0.5) for the stiffness of the compromised vessels was used as a threshold for the maximal output force. Finally, finite element analysis (FEA) was conducted to study the stress distribution in the first design. A sample prototype was then printed and assembled for initial testing. Results: The Gecko Hands design was chosen for its minimization of compressive force, as well as its integration of aspiration. The proposed design meets the selection criteria of current forceps (21.6cm, 24g, < 10N applied force) and also employs the use of suction to remove excess fluid in the surgical space. In doing so, the Gecko Hands vacuum forceps also replaces the surgical aspirator, another commonly used surgical device. The use of this multi-tool in CABG surgery could eliminate surgical clutter during openheart procedures while also reducing the duration of surgery
Second Annual IEEE Medical Device Symposium
“Medical Device Innovation in 21st Century”
The University of Texas at Dallas, Richardson, TX.
Metal-on-Metal Total Hip Implants: A Study Their Failure Modes in Relation
to Adverse Local Tissue Reaction
*Maria Burbano1; Izabelle M. Gindri
1; Robert D. Russell
2; Michael H. Huo
2;
Danieli Rodrigues1
Introduction: The use of metal-on-metal (MoM) total hip arthroplasty (THA) has decreased recently due
to concerns of high failure rates. MoM hip implant designs have shown to generate metal debris particles
that are released into the surrounding soft tissues. These released contaminants have caused inflammatory
reactions in the patients know as adverse local tissue reactions (ALTR).
Aims and Methods: The purpose of this study was to characterize failure patterns in retrieved MoM
THA components revised for ALTR. Four retrieved MoM THA components were selected for analysis
from an ongoing retrieval study due to the presence of ALTR. All specimens were analyzed using digital
microscopy. Particularly corroded and scratched areas were further analyzed under Scanning Electron
Microscopy (SEM), and Energy Dispersive X-ray Spectrometer (EDS).
Results and Conclusions: All patients were revised for pain and presence of ALTR (range 23-134
months in vivo). Surface analysis revealed three distinct failure mechanisms: 1) corrosion at the head-
neck junction, 2) mechanical wear at the head-cup bearing surface with severe scratching, and 3) pitting
attack, induced by reduction in surface potential due to scratching. The implant with the most severe wear
had a cup abduction angle of 57 degrees. The implant with the most significant corrosion at the head-neck
junction was a 32-mm CoCr head on a titanium alloy stem.
Multiple failure mechanisms of MoM THA implants exist, including corrosion, mechanical wear,
and pitting. Increased metal ion levels and ALTR were present in patients with these failure mechanisms.
In response to clinical observations of implant performance, a novel surface treatment technology to
improve lubrication and corrosion properties of these MoM implants is under investigation.
1Department of Bioengineering, University of Texas at Dallas, Richardson, TX
*Email of authors are listed in sequential order as listed above under their corresponding affiliations.
A Software for Analyzing Brain’s Dynamic Functional Connectivity from Functional Magnetic Resonance Images Johnny Esquivel, Mutlu Mete, Unal “Zak” Sakoglu Department of Computer Science Texas A&M University - Commerce Commerce, TX, USA [email protected], [email protected], [email protected] I. INTRODUCTION
Functional magnetic resonance imaging (fMRI) is a medical imaging method which measures brain activity by detecting changes in blood-oxygenation levels. Functional connectivity analyses investigate interactions among different brain regions using fMRI data. These interactions are very dynamic; this necessitates the use and implementation of dynamic functional connectivity (DFC) methods. There is need for user-friendly software which implements these methods. II. AIMS AND METHODS
The software is implemented as a graphical user interface (GUI) written in MATLAB. It can read 4D-Nifti fMRI data, different brain maps and atlas files which labels different anatomical regions and it can do co-registration between atlas and data. Functional connectivity among different networks or regions from the data are calculated dynamically by calculating the correlation among time-courses using a sliding time-window. The window step size and width are adjustable through the GUI. The dynamics of the connectivity can be plotted, along with any experimental tasks/stimuli. This allows quantification of how connectivity is modulated by task/stimuli, if any. The GUI allows the user to identify functionally connected brain networks or regions both visually and numerically. Numerically, it can list highest correlated brain network/region combinations. Visually, it can show the brain images with the highlighted networks/regions. DFC analysis can be applied to any fMRI data directly; however, it can also be applied to networks found by independent component analysis (ICA). ICA is a blind source-separation technique used for separating independent brain networks. ICA results can be also be loaded and analyzed with our software which can identify the most significant connections among brain networks. III. RESULTS AND CONCLUSIONS
The user-friendly DFC GUI implements analysis methods for quantifying the dynamics of the brain’s functionally connected regions or networks from fMRI data. It also features tools for visualizing functionally-connected networks, functional connectivity dynamics and task-modulation.
A Software for Multivoxel Pattern Analysis of Functional Magnetic Resonance
Functional magnetic resonance imaging (fMRI) is a medical imaging method which indirectly measures brain activity by measuring changes in blood-oxygenation levels from 3D snapshots of the brain every few seconds. Exposing a subject to different kind of stimuli or tasks systematically during the fMRI scan causes different parts of the brain to activate. FMRI signal can be analyzed to find out the characteristics of these activations and any systematic activation differences under different stimuli/tasks. Multivariate pattern recognition and classification algorithms, as known as multivoxel pattern analyses (MVPA) methods in the neuroimaging community, have been recently applied to fMRI data to classify between different brain “states” or “conditions” resulting from different stimuli/tasks. MVPA methods have been gaining popularity in neuroimaging and there is need for user-friendly graphical user interface (GUI) software which implements these methods.
II. AIMS AND METHODS
In this project, we implemented in MATLAB a GUI tool which can read 4D-Nifti fMRI data from the brain, and does classification of different brain “states” or “conditions” using various supervised machine learning algorithms. The algorithms which are implemented in the toolbox include linear discriminant analysis, neural networks, logistic regression, sparse multinomial logistic regression, ridge regression, and support vector machines. The toolbox allows the user to mask the brain and focus on only the anatomical parts she/he is interested in. The tool accommodates choosing between various types of inputs which describe the fMRI experiment stimuli/tasks and it provides a detailed visualization of results.
III. RESULTS AND CONCLUSIONS
A user-friendly GUI software which implements multivoxel pattern analysis or machine learning methods for classifying different brain states or conditions from the fMRI data is developed. It enables fast and efficient classification analysis of large-scale fMRI data from multiple subjects and it provides effective visualization of these classification results for better interpretation.
Future biomedical devices may enable chronic sensing or stimulation of body tissue through stable
interfaces between soft tissue and high-performance electronics. We demonstrate flexible organic
thin-film transistors (OTFTs) on physiologically-responsive smart polymer substrates with shape-
changing and softening properties that can mechanically-adapt after implantation for creating soft
bioelectronic interfaces.
Shape memory polymers (SMPs) are smart polymers which respond to stimuli, such as a temperature
change, to soften and change shape. Here, we synthesize SMP substrates which can adapt in vivo to
autonomously form secure interfaces with target tissue. The thiolene-acrylate shape memory polymer
(SMP) substrate exhibits a drop in modulus of over two orders of magnitude when exposed to
physiological conditions, reducing the modulus mismatch with soft tissue. Reduction in the
mechanical mismatch between biomedical implants and soft tissue through soft materials has been
shown to extend the long-term viability of biotic/abiotic interfaces. Additionally, large 3D shape
changes are enabled based on the release of stored applied stresses for creating deployable structures,
or the conforming of films to 3D geometries.
OTFTs fabricated on SMP substrates are demonstrated which can autonomously deploy to programmed 3D shapes 15× larger than the insertion footprint of the device, as well as conform to 3D surfaces with radii as small as 500 μm. Acute in vivo stability of a conformable OTFT is shown with only small changes in device performance after implantation for 24 hours. Flexural stability of the OTFTs is demonstrated down to 1 mm radius for four bending configurations; with some devices remaining operational at radii as small as 100 μm. The flexible low-voltage transistors (3 V) based on the air-stable organic semiconductor, dinaphtho[2,3-b:2’,3’-f]thieno[3,2-b]thiophene (DNTT), are demonstrated with a measured average mobility of 1.5 cm2V-1s-1 and an on/off current ratio of 104, which is suitable for sensing small biosignals at low operating voltages.
Abstract: Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects almost two million people every year. The effects of TBI include weakness and loss of coordination, and these effects can be observed even years after the initial injury. We have developed a method by which we drive cortical plasticity through stimulation of the vagus nerve during rehabilitative therapy to assist recovery from TBI. We trained rats to perform the isometric pull task – a skilled reaching and strength task. After training, all animals received a controlled cortical impact in the forelimb area of left motor cortex. After injury, one group of animals received vagus nerve stimulation (VNS) paired with rehabilitative therapy, while another group received rehabilitative therapy alone. We found that animals that received VNS paired with therapy achieved a full recovery of their forelimb strength, while animals that received only rehabilitative training did not significantly recover forelimb strength. Author: David Pruitt The University of Texas at Dallas Cognition and Neuroscience [email protected] Supervising Investigator: Dr. Robert L. Rennaker II The University of Texas at Dallas Associate Professor [email protected]
Stroke is a debilitating neurological disease that affects 800,000 individuals in the United States
each year, with many of these patients suffering chronic motor impairments. The development of
treatment strategies to restore motor function after stroke represents a significant unmet clinical need.
We have recently developed a technique to improve motor function after stroke based on stimulation of
the vagus nerve paired with rehabilitative training. Our previous studies have demonstrated that vagus
nerve stimulation (VNS) paired with rehabilitative training improves recovery of multiple parameters of
forelimb function in a model of ischemic stroke in young rats.
Aims and Methods:
We sought to evaluate if VNS paired with rehabilitative training would improve recovery of
forelimb function in two models of stroke that share more characteristics with the clinical population of
stroke patients, including subcortical brain damage and in the context of advanced age. In the first
experiment, a cohort of rats was trained to proficiency on the bradykinesia assessment task, a novel
behavioral task that measures multiple parameters of forelimb function, and then underwent a unilateral
hemorrhagic stroke to severely impair function of the trained limb. Subjects subsequently received
rehabilitative training with or without VNS and recovery of skilled forelimb function was measured. In the
second experiment, a cohort of aged rats (18 months old) were trained to proficiency on the isometric
force task and then underwent a unilateral ischemic stroke to impair the trained forelimb. Subjects
subsequently received rehabilitative training with or without VNS and recovery of forelimb strength was
measured.
Results and Conclusions:
Here we show that VNS paired with rehabilitative training improves recovery of forelimb function
in a model of severe hemorrhagic stroke. Additionally, preliminary findings suggest that VNS paired with
rehabilitative training improves recovery of forelimb strength in aged rats. Our results indicate that VNS
enhances recovery after stroke in two models that bear similarity to the clinical population of stroke
patients; therefore, VNS represents a potential therapy to increase motor recovery in stroke patients.
Zinc Oxide-based Nanosensor for the Ultra-sensitive
Detection of Troponin-T
Michael Jacobsa, Sriram Muthukumarb, Shalini Prasada
a. Department of Bioengineering
b. Department of Materials Science and Engineering
University of Texas at Dallas
Richardson, Texas, USA
Introduction This project demonstrates the development of a zinc oxide based microelectrode sensor for the ultra-sensitive detection of protein biomarkers. Biomarkers are unique biological macromolecules that may indicate the presence or risk of certain developing ailments. Point-of-care, rapid quantification of these molecules is essential to disease identification, monitoring, and analysis. Currently employed technologies for quantitative detection of protein biomarkers suffer from problems such as a lack of sensitivity/selectivity, dominance of signal noise, adaptability of detection to a wide range of biomolecules, and are not geared for rapid detection. Our research focuses on utilizing a materials-based approach to overcome these problems often associated with the detection of biomarkers by utilizing zinc oxide as part of our biosensor for (1) improved binding surface area for enhancing sensitivity and (2) creating nano-structures for biomolecule confinement that can enhance output signal response. Aims and Methods This study integrated nanotextured zinc oxide thin films onto printed circuit boards using RF magnetron sputter deposition at room temperature. By manipulating zinc oxide deposition conditions, certain properties of the material can be tuned to increase the efficacy of signal transduction. These fabrication conditions not only dictate the number of oxygen vacancies within the film but also regulate the amount of zinc and oxygen terminated ends occurring on the material surface. Zinc oxide films sputtered with and without the presence of oxygen were examined for possible differences in biosensor efficacy. Evaluation of the cross-linkers dithiobis succinimidyl propionate and (3-aminopropyl)triethoxysilane for binding to these two different surfaces was achieved through fluorescent studies. Qualitative and quantitative assessment of cross-linker binding was accomplished using microscopy and fluorescent intensity measurements. Impedance spectroscopy was used as the electrical transduction mechanism for detection of the well-established cardiac biomarker, troponin-T, whose presence in trace quantities is indicative of multiple cardiovascular ailments. Results and Conclusion This study focuses on the correlation between the effect of physical confinement and surface
termination of nanotextured zinc oxide to its performance as a biosensor. Troponin-T was detected as
low as 10 fg/mL in purified buffer media and 100 fg/mL in human serum. The zinc oxide films sputtered
without the presence of oxygen showed enhanced detection due to oxygen vacancies within the film
and a greater amount of cross-linker binding to the surface of the sensing site. This platform
demonstrates applicability as a sensitive, low-cost, rapid and easy to use tool that can be integrated as a
point-of-care diagnostic device.
Movement-paired vagus nerve stimulation improves motor
recovery following ischemic brain damage
Daniel Hulsey1, Navid Khodaparast1,2, Seth Hays1,2,*, Andrew Sloan1,2, Andrea Ruiz1, Priyanka
An automated supination assessment task Eric Meyers1, Anil Sindhurakar3, Seth Hays2, Robert Rennaker1,2, Andrew Sloan2, Jason Carmel3,
Michael Kilgard1
1The University of Texas at Dallas, Erik Jonsson School of Engineering and Computer Science, 800 West Campbell Road, Richardson, TX 75080-3021 2The University of Texas at Dallas, School of Behavior and Brain Sciences, 800 West Campbell Road, Richardson, TX 75080-3021 3Burke Medical Research Institute, Motor Recovery Laboratory, 785 Mamaroneck Avenue, White Plains, NY 10605
Introduction:
Loss of motor function following stroke affects hundreds of thousands each year. Many stroke patients
who have motor loss experience some level of impaired distal wrist rotation. The current gold standard tasks of measuring distal rotation in rodents are prone to human error and problems in different scoring
systems. There is currently no task that allows a quantitative measurement of supination and pronation in rodents.
Aims and Methods:
We have developed a novel behavioral task that allows us to automate and quantitatively measure distal
forelimb supination in rats. The task requires animals to reach through a small aperture in a clear acrylic cage, grasp a spherical knob, and then supinate. The knob is attached to a rotary encoder and allows
measurements of ¼” of a degree. When the user defined threshold is reached, the animal is rewarded with a pellet. The data is displayed in real time and recorded automatically. With a rich dataset of 300-
400 trials a day per animal, we can quantitatively analyze each rat’s performance free from human bias.
Due to the automation of the program, and implementing adaptive hit thresholds, we are able to train animals to proficiency within two weeks. Once the animals trained to the specified degree threshold,
unilateral motor cortex ischemic lesions are administered.
Results and Conclusions: Animals exhibit a sustained supination deficit following motor cortex ischemia. All relevant calculated
parameters show a drop in performance, including total degrees turned, velocity, acceleration, and inner
spin times. Our results show that our task isolates distal rotation and is a sensitive measurement of supination loss.
Measuring Forelimb Speed on a Skilled Reaching Task in 6-OHDA lesioned rats Anthony Nguyen, Seth Hays Ph.D., David Pruitt, Michael Kilgard Ph.D., Robert Rennaker Ph.D. Introduction The bradykinesia assessment task, is a modified appetitive skilled reaching task in which rats are trained to press a lever twice in rapid succession. The bradykinesia assessment task demonstrates a reduction in performance of multiple parameters of forelimb function, including a decrease in forelimb movement speed, resulting from both hemorrhagic striatal lesions and ischemic lesions to the motor cortex. Rat models of PD utilize the stereotaxic administration of the neurotoxin 6-OHDA into the medial forebrain bundle to cause extensive damage to the dopaminergic neurons of the substantia nigra. We hypothesized that 6-OHDA lesioned animals would show deficits in multiple parameters of forelimb function on the bradykinesia assessment task. Aims To assess the sensitivity of the bradykinesia assessment task to a unilateral 6-OHDA lesion to the medial forebrain bundle (MFB), the predominant model for preclinical research of Parkinson's disease. Methods After training the animals to task proficiency, unilateral infusions of 6-OHDA into the medial forebrain bundle were performed to induce Parkinson’s disease. Motor performance on the bradykinesia assessment task was continued for 6 weeks post-lesion. The lever was attached to a electrical potentiometer. This allowed us to obtain an analog signal of the position of the lever. Using custom software, we were able to quantitatively analyze multiple parameters of forelimb function. Results After administration of 6-OHDA, the rats showed an impairment in forelimb speed, and marked reduction in successful trials, total presses per trial, and total trials per session. Discussion This study assessed the sensitivity of the bradykinesia assessment task on unilateral 6-OHDA lesions to the medial forebrain bundle. The 6-OHDA lesioned rats showed marked declines in multiple parameters of forelimb function. This task produced deficits in rats with sub-maximal nigral damage, which could be analogous to subclinical neuronal changes in the Parkinsonian brain and warrants further investigation. Authors Anthony Nguyen The University of Texas at Dallas [email protected] Seth Hays Ph.D. The University of Texas at Dallas [email protected] David Pruitt The University of Texas at Dallas [email protected] Michael Kilgard Ph.D. The University of Texas at Dallas [email protected] Robert Rennaker Ph.D. The University of Texas at Dallas [email protected]
The research objective is to design a wireless transponder for antenna-based sensors used to
simultaneously measure shear and pressure forces for diabetic foot diagnosis. The transponder
is placed on the top surface of a shoe and consists of sensors and an interrogation system that
transmits information to a receiver by modulating the interrogation frequency. The identification
system includes an energy harvester, crystal oscillator and a passive mixer. A single chip
interrogation circuit has been designed in CMOS to reduce size.
Aims and Methods:
The sensors can be interrogated based on the principle of backscattering. A Rx/Tx antenna
connects to the sensor via a switch. The Rx/TX antenna receives an interrogation signal that is
either reflected by the switch or antenna sensor. When the switch is controlled using an
oscillator, the reflected signal will be amplitude-modulated at the oscillator frequency. The RF
energy harvester IC consists of a rectifier, limiter, reference and voltage regulator designed to
power up the oscillator since it is the only device which needs an external power source. The
rectifier converts the RF signal to DC and powers up the entire identification blocks. The voltage
regulator generates a clean and regulated signal for the crystal oscillator.
Results:
The proposed identification system was fabricated in IBM 130nm CMOS technology. The
rectifier generates a DC voltage up to 1.75V with an applied
7dBm signal at 5.8GHz. The limiter maintains DC voltage to 1.2V and powers up the entire
system. The limiter is followed by a voltage reference and regulator circuits to provide 0.6V
supply voltage for the crystal oscillator. The crystal oscillator, including the output buffer and
level shifter, generate 4MHz signals with 0.8 Vp-p amplitude for the passive mixer with 15dBm of
conversion loss. The identification system including bond pads has a size of 1.2mm × 0.8mm.
I. E-VEST: ATHLETIC HEART MONITORING SYSTEM
By Rizan Shrestha, Jeff Smith, Miguel Ysuhuaylas, and Ryan Johnson
II. INTRODUCTION
Sudden cardiac arrest is a condition in which proper heart function seizes unexpectedly (often due to ventricular fibrillation) and often results in death without immediate medical attention. When an athlete performs vigorous workout sessions, a sudden cardiac arrest could happen, resulting in sudden cardiac death (SCD).
III. AIM AND METHOD
The aim of our project is to design and implement an electrocardiogram (ECG) monitoring device, which monitors athletes’ ECG signals autonomously. The system is latched inside a wearable vest which monitors the signal from an athlete. It processes the analog signal through a microcontroller and then sends the collected real time data wirelessly to a base station. The base station will further process the digital signal through various filters to acquire a reasonably clean ECG signal while checking for any sort of abnormality, which can trigger an alarm to the nearest emergency unit from where the athlete is located.
IV. RESULTS AND CONCLUSION
Modern automatic external defibrillators (AEDs) substantially increase the survival rate from sudden cardiac arrest during marathon runs, but current responses are typically ‘de facto’ and require experienced EMS personnel to identify and then treat sudden cardiac arrest. Therefore, athletes may be willing to wear an E-vest that can automatically recognize a cardiac event and immediately alert EMS and/or exercise event emergency personnel. We are currently working on reducing the noise on the transmitted signal in the analog domain via notch-filtering. We are also working on further noise reduction in the digital domain using various finite impulse response (FIR) filters. The end goal is to attenuate noise and produce a clean signal. Once we achieve this goal, we will perform multiple analysis tests on multiple human cardiac signals. We are expecting to minimize the size and weight of the circuit for minimal intrusion and maximum comfort.
DESIGN AND FABRICATION OF NANOGAP FOR BIOSENSING APPLICATIONS Meghana Pamidighantam and Dr Shalini Prasad
Department of Bioengineering, University of Texas at Dallas
Hearing loss is the most common chronic disorder in the world, impairing more people than
blindness, heart disease and cancer combined. Currently, hearing can be partially restored through
cochlear implants (CIs) which bypass cochlear dysfunction through direct electrical stimulation of
spiral ganglion neurons (SGNs). These devices are limited by their low frequency and intensity
resolution of sound coding, a result of inadequate electrode contact to stimulate the SGNs. Moreover,
insertion of standard CI arrays cause trauma to both the basilar membrane and lateral wall of the
cochlea, resulting in an inflammatory response and trauma which ultimately leads to fibrosis and
neo-ossification.
We propose to utilize temperature dependent shape memory polymers to fabricate cochlear implants.
Specifically, the shape memory effect allows for stiff insertion of cochlear implants that soften and
coil during implantation, are chronically flexible and are compatible with photolithography. As the
CI warms to body temperature, it transitions to the “remembered” coiled shape of the cochlea and
atraumatically navigates the turns of scala tympani. Beyond improving substrate design to achieve
enhanced stimulation of SGNs, we aim to overcome modern challenges to CI design regarding
electrode size and charge injection capacity. By utilizing materials such as titanium nitride or
PEDOT in order to increase the porosity of electrode surfaces, we seek to attain an electrochemical
surface area many times larger than the geometric surface area. In this way, we can increase the
number of electrodes within the same geometric area, maintaining comparable charge injection levels
while increasing signal specificity to SGNs to improve sound coding.
The results of this study are intended to enable improved cochlear stimulation and can be applied to a
host of flexible neural electronics such as cortical probes, regenerative nerve electrodes and nerve
cuff electrodes.
Raising the Core Body Temperature by Heating Glabrous Surfaces During Vasodilation By: Andrew Stier Intro: Anesthesia can prevent the blood vessels from constricting, increasing blood perfusion and allowing blood cooled by the cold ambient air to travel to and cool down the core. Operating on a patient with a hypothermic core can cause complications. This experiment involves a solution to this dilemma. Aims and Methods: This experiment aims to show experimental evidence supporting the theory that supplying a high amount of heat to the palms of the hands and the soles of the feet while inducing increased blood perfusion can raise the core body temperature and sustain it at a desired level. The palms and soles are glabrous skin surfaces which have been shown to be areas of great heat transfer during vasodilation and increased blood perfusion. This heat must be supplied with a heating device that is flexible, completely adhesive, and able to supply uniform heat to avoid burning the patient. This project involved fabricating a surface electronic heater that meets these criteria using nanofabrication techniques. A prototype of this device was created by spincoating polyimide (PI) onto a glass slide. Ultra thin titanium wires were then sputtered onto the slide using sputtering, photolithography, and a mask designed in SolidWorks. The wires were then bonded to an external voltage source using thin flexible cables, and produce heat when voltage is applied. Once perfected, this prototype can be used to test the theory. Results and Conclusions: Applying 45V of voltage to the device allowed it to reach sufficiently high temperatures (up to 43oC). In future prototypes, gold may be used in place of titanium as it has a lower resistivity constant and should reach higher temperatures at lower voltages. Future prototypes will be transferred to temporary tattoo adhesive sheets so that the device can be applied to the skin in a flexible, low pressure manner. Affiliations: Dr. Kenneth Diller, Dr. Nanshu Lu, Yalin Yu Email address: [email protected]